Study of Romosozumab (AMG 785) Administered to Healthy Participants and Patients With Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Hemodialysis

Amgen24 enrolled

Overview

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity profile of romosozumab after a single 210 mg subcutaneous dose in healthy participants and patients with stage 4 renal impairment (RI) or stage 5 RI requiring hemodialysis.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Osteoporosis

Interventions

RomosozumabDRUG

Administered as three 70 mg/mL prefilled syringe injections

Eligibility

Sex: ALLMin age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

INCLUSION CRITERIA - ALL SUBJECTS : * Males or females ≥ 50 years of age * Body weight ≥ 45 and ≤ 110 kg * Willing to adhere to calcium and vitamin D supplementation requirements * Females must be of non-reproductive potential INCLUSION CRITERIA - SUBJECTS WITH RENAL IMPAIRMENT (GROUPS 1 AND 2): * Group 1 - Stage 4 RI (estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m²) * Group 2 - End stage renal disease requiring hemodialysis INCLUSION CRITERIA - HEALTHY SUBJECTS (GROUP 3): • Renal function defined as an estimated glomerular filtration rate (eGFR) ≥ 80 mL/min/1.73 m² EXCLUSION CRITERIA - ALL SUBJECTS: * History of metabolic or bone disease (except for metabolic bone disease in renal impairment (RI) subjects) * History of osteoporosis, vertebral fracture, or fragility fracture of the wrist, humerus, hip, or pelvis after age 50 * Recent bone fracture * Vitamin D insufficiency * Hypocalcemia or hypercalcemia * Hypomagnesemia * Hypophosphatemia * Untreated hyper- or hypothyroidism * Females with a positive pregnancy test * Males with pregnant partners * Females who are lactating/breastfeeding or plan to breastfeed on study and for 3 months after receiving the dose of study drug * History of spinal stenosis * History of facial nerve paralysis * Positive for human immunodeficiency virus (HIV) antibodies * Positive for hepatitis B surface antigen or detectable hepatitis C * Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical, or breast ductal carcinoma in situ) within 5 years before screening * History of solid organ or bone marrow transplants EXCLUSION CRITERIA - HEALTHY SUBJECTS (GROUP 3) * Current hyper- or hypoparathyroidism

Locations (5)

Research Site

Tempe, Arizona, United States

Research Site

Los Angeles, California, United States

Research Site

Denver, Colorado, United States

Research Site

Pembroke Pines, Florida, United States

Outcomes

Primary Outcomes

Number of Participants With Adverse Events

A serious adverse event was defined as an adverse event (AE) that met at least 1 of the following serious criteria: * fatal * life-threatening * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. A treatment-related adverse event (TRAE) was an AE assessed by the investigator as possibly related to the study drug, indicated by a "yes" response to the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?"

Time frame: From the first dose of study drug up to day 85

Number of Participants Who Developed Anti-Romosozumab Antibodies

Two validated assays were used to detect the presence of anti-romosozumab antibodies. First, an electrochemiluminescent immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Second, a non-cell-based competitive binding bioassay was used to test positive binding antibody samples for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.

Time frame: Baseline and day 85

Albumin-Adjusted Serum Calcium Concentrations by Visit

Albumin-adjusted calcium was derived as: Where serum albumin \< 40 g/L then albumin-adjusted calcium = measured total calcium (mmol/L) + 0.02 \* \[40 - serum albumin (g/L)\]; Where serum albumin ≥ 40 g/L then albumin-adjusted calcium = measured total calcium.

Time frame: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit

Intact Parathyroid Hormone (iPTH)Concentrations by Visit

Time frame: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit

Secondary Outcomes

Data from ClinicalTrials.gov

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